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Evidence-Based Recommendations for the Diagnosis and Treatment of Pediatric
Acne
Lawrence F. Eichenfield, Andrew C. Krakowski, Caroline Piggott, James Del Rosso,
Hilary Baldwin, Sheila Fallon Friedlander, Moise Levy, Anne Lucky, Anthony J.
Mancini, Seth J. Orlow, Albert C. Yan, Keith K. Vaux, Guy Webster, Andrea L.
Zaenglein and Diane M. Thiboutot
Pediatrics 2013;131;S163
DOI: 10.1542/peds.2013-0490B
The online version of this article, along with updated information and services, is
located on the World Wide Web at:
http://pediatrics.aappublications.org/content/131/Supplement_3/S163.full.html
PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly
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of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.
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SUPPLEMENT ARTICLE
Evidence-Based Recommendations for the Diagnosis
and Treatment of Pediatric Acne
AUTHORS: Lawrence F. Eichenﬁeld, MD,a Andrew C.
Krakowski, MD,a Caroline Piggott, MD,a James Del Rosso,
DO,b Hilary Baldwin, MD,c Sheila Fallon Friedlander, MD,a
Moise Levy, MD,d Anne Lucky, MD,e Anthony J. Mancini, MD,f
Seth J. Orlow, MD, PhD,g Albert C. Yan, MD,h Keith K. Vaux,
MD,i Guy Webster, MD, PhD,j Andrea L. Zaenglein, MD,k,l and
Diane M. Thiboutot, MDl
aDivision of Pediatric and Adolescent Dermatology, Rady
Children’s Hospital, San Diego and Departments of Pediatrics and
Medicine (Dermatology), University of California, San Diego, San
Diego, California; bSection of Dermatology, Valley Hospital
Medical Center, Las Vegas, Nevada; cDepartment of Dermatology,
SUNY Downstate Medical Center, Brooklyn, New York; dPediatric/
Adolescent Dermatology, Dell Children’s Medical Center, Austin,
Texas, Department of Dermatology, UT Southwestern Medical
School, Dallas, Texas and Departments of Pediatrics and
Dermatology, Baylor College of Medicine, Houston, Texas;
eDepartments of Dermatology and Pediatrics, University of
Cincinnati College of Medicine and Cincinnati Children’s Hospital
Medical Center, Cincinnati, Ohio; fDepartments of Pediatrics and
Dermatology, Northwestern University Feinberg School of
Medicine and Division of Dermatology, Ann & Robert H. Lurie
Children’s Hospital of Chicago; gThe Ronald O. Perelman
Department of Dermatology, New York University School of
Medicine, New York, New York; hSection of Pediatric Dermatology,
Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania
and Departments of Pediatrics and Dermatology, Perelman
School of Medicine at the University of Pennsylvania;
iDivision of Pediatrics and Hospital Medicine, Rady Children’s
Hospital, San Diego, California and Department of Pediatrics,
University of California, San Diego, California; jDepartment of
Dermatology, Jefferson Medical College, Thomas Jefferson
University, Philadelphia, Pennsylvania; kDepartment of
Dermatology, The Pennsylvania State University College of
Medicine; and lDepartment of Pediatrics, Penn State Hershey
Children’s Hospital, Hershey, Pennsylvania
KEY WORDS
pediatric acne, acne treatment, combination acne therapy,
retinoids, benzoyl peroxide, bacterial resistance, isotretinoin,
hormonal therapy, acne guidelines, acne algorithm, neonatal
acne, infantile acne, mid-childhood acne, preadolescent acne,
American Acne and Rosacea Society, AARS
(Continued on last page)
abstract
INTRODUCTION: Acne vulgaris is one of the most common skin conditions in children and adolescents. The presentation, differential diagnosis, and association of acne with systemic pathology differs by
age of presentation. Current acknowledged guidelines for the diagnosis and management of pediatric acne are lacking, and there are
variations in management across the spectrum of primary and specialty care. The American Acne and Rosacea Society convened a panel
of pediatric dermatologists, pediatricians, and dermatologists with
expertise in acne to develop recommendations for the management
of pediatric acne and evidence-based treatment algorithms.
METHODS: Ten major topic areas in the diagnosis and treatment of
pediatric acne were identiﬁed. A thorough literature search was performed and articles identiﬁed, reviewed, and assessed for evidence
grading. Each topic area was assigned to 2 expert reviewers who developed and presented summaries and recommendations for critique
and editing. Furthermore, the Strength of Recommendation Taxonomy,
including ratings for the strength of recommendation for a body of
evidence, was used throughout for the consensus recommendations
for the evaluation and management of pediatric acne. Practical
evidence-based treatment algorithms also were developed.
RESULTS: Recommendations were put forth regarding the classiﬁcation, diagnosis, evaluation, and management of pediatric acne, based
on age and pubertal status. Treatment considerations include the use
of over-the-counter products, topical benzoyl peroxide, topical
retinoids, topical antibiotics, oral antibiotics, hormonal therapy, and
isotretinoin. Simpliﬁed treatment algorithms and recommendations
are presented in detail for adolescent, preadolescent, infantile, and
neonatal acne. Other considerations, including psychosocial effects
of acne, adherence to treatment regimens, and the role of diet and
acne, also are discussed.
CONCLUSIONS: These expert recommendations by the American Acne
and Rosacea Society as reviewed and endorsed by the American Academy of Pediatrics constitute the ﬁrst detailed, evidence-based clinical
guidelines for the management of pediatric acne including issues of
special concern when treating pediatric patients. Pediatrics 2013;131:
S163–S186
PEDIATRICS Volume 131, Supplement 3, May 2013
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S163
Acne vulgaris is one of the most common skin conditions in children and
adolescents. Although often considered
a disease of teenagers, in whom the
prevalence is reported to be from 70%
to 87%,1 12 years of age is no longer
considered the lower end of the age
range for acne onset.2 A study by Lucky
et al3 revealed acne lesions in 78% of
365 girls ages 9 to 10. In addition, acne
and other acneiform (acnelike) conditions occur at different ages, including neonates, infants, and young
children, and may be associated with
differential diagnoses or systemic pathology that differs from teenagers.
There are issues of special concern in
treatment of preadolescents with acne.
The majority of clinical trials for acne
medications are conducted in patients
12 years of age or older. As a result,
there is little published evidence regarding the safety and efﬁcacy of many
acne medications in pediatric patients.
Furthermore, the treatment of acne
often involves use of several medications that target either different types
of acne lesions, different factors involved in the pathogenesis of acne, or
different degrees of acne severity. Potential interactions between medications can add another layer of
complexity to the management of acne
in pediatric patients, as can concerns
about systemic side effects and impact
of medications on growth and development. The psychosocial impact of
acne can be signiﬁcant, as can issues of
adherence to treatment regimens.
Currently, detailed, acknowledged guidelines for the diagnosis and management of acne in pediatric patients are
lacking. Recognizing the need to address special issues regarding the
diagnosis and treatment of acne in
children of various ages, a panel of
experts consisting of pediatric dermatologists, pediatricians, and dermatologists with expertise in acne was
convened under the auspices of the
S164
American Acne and Rosacea Society,
a nonproﬁt organization promoting
research, education, and improved
care of patients with acne and rosacea.
The expert panel was charged with
developing recommendations for the
management of pediatric acne and
evidence-based treatment algorithms.
A member of the expert panel served as
liaison to the American Academy of
Pediatrics and as part of the recommendation writing group.
METHODS
The expert panel identiﬁed special
issues in the diagnosis and treatment of
acne and acneiform conditions in pediatric patients across various ages.
Ten major topic areas were speciﬁed by
the panel (Table 1). A thorough Englishlanguage literature search was performed for each topic area, and identiﬁed
articles were reviewed utilizing a
patient-centered approach to grading
evidence available to the expert panel.4
Relevant clinical trial registries and
data ﬁled with the Food and Drug Administration (FDA) were included in the
data review.
TABLE 1 Topic Areas Researched and
Discussed by Expert Panel
Pediatric Acne Categorization and Differential
Diagnosis of Acne
Evaluation of Pediatric Acne by Age/Classiﬁcation
Evidence-based Treatment Review for Pediatric
Acne
• OTC products
• BP treatment
• Topical retinoids, antibiotics, and ﬁxed-dose
combination products
• Oral antibiotics: age-related issues, safety, and
resistance
• Isotretinoin pediatric patients with severe acne
• OC use and hormonal therapy
Pediatric Acne Treatment Considerations
• Previous treatment history
• Costs
• Ease of use/regimen complexity and adherence
• Vehicle selection
• Active scarring
• Side effects
• Psychosocial impact
• Diet
Each topic area was assigned to 2 expert reviewers, who developed and
presented an in-depth summary and
recommendations for further critique
and editing. The Strength of Recommendation (SOR) Taxonomy ratings for
the recommendation for a body of evidence is noted throughout the article.4
This taxonomy addresses the quality,
quantity, and consistency of evidence
and allows authors to rate individual
studies or bodies of evidence. The taxonomy emphasizes the use of patientoriented outcomes that measure
changes in morbidity or mortality. The
authors reviewed the bodies of evidence for each of the recommendations and assigned one of the following
SOR: an A-level recommendation is
based on consistent and good-quality
patient-oriented evidence; a B-level
recommendation is based on inconsistent or limited-quality patient-oriented
evidence; and a C-level recommendation is based on consensus, usual
practice, opinion, disease-oriented evidence, or case series for studies of
diagnosis, treatment, prevention, or
screening. This article summarizes the
resultant consensus recommendations for the evaluation and diagnosis
of pediatric acne, as well as a series of
treatment algorithms to assist health
care practitioners in the management
and treatment of acne in pediatric
patients.
CATEGORIZATION AND
DIFFERENTIAL DIAGNOSIS OF
PEDIATRIC ACNE
Both age and form of presentation are
relevant to the diagnosis of pediatric
acne. Although there is some overlap in
age and presentation of acneiform
conditions, the consensus of the panel
regarding relevant age categories is
presented in Table 2. These ranges are
approximate. In girls, age of onset of
menarche may be a better delineating
point between preadolescence and
EICHENFIELD et al
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SUPPLEMENT ARTICLE
TABLE 2 Expert Panel Consensus: Pediatric
Acne Categorized by Age
Acne Type
Age of Onset
Neonatal
Infantile
Mid-childhood
Preadolescent
Birth to #6 wk
6 wk to #1 y
1 y to ,7 y
$7 to #12 y or menarche
in girls
$12 to #19 y or after
menarche in girls
Adolescent
adolescence. In general, acne is uncomplicated by systemic disease, but
in some cases it may be a cutaneous
manifestation of underlying pathology.
It is essential to have a broad understanding of acne at different ages
and to be aware of the differential diagnoses for each age group. Table 3
presents a differential diagnosis for
acne in each age group.5–7 Workup is
based on age and physical ﬁndings.6
The physical examination should focus
on type and distribution of acne
lesions, height, weight, growth curve,
and possible blood pressure abnormalities. Signs of precocious sexual
maturation or virilization should prompt
workup and/or a referral to a pediatric
endocrinologist.8
Consensus Recommendation:
Acneiform eruptions from the neonatal period through adolescence
may be broadly categorized by age
and pubertal status.
cheeks, chin, eyelids, and forehead, but
the scalp, neck, and upper chest and
back may be involved.8 Its pathogenesis may involve colonization with
Malassezia species, a normal commensal of infant skin, or may represent
an inﬂammatory reaction to a yeast
overgrowth at birth.8,10 NCP is typically
mild and self-limited, and reassuring
the parents is usually the only management needed. If lesions are numerous, 2% ketoconazole cream may
reduce fungal colonization.11 Newborns also may present with or develop
transient neonatal pustular melanosis,
with pustules on the chin, neck, or
trunk. Within 24 hours, these pustules
rupture, leaving hyperpigmented macules with a rim of faint white scale.10
Consensus Recommendation:
Neonates may have true acne, although many self-limited papulopustular eruptions also occur on
the faces of neonates. In infants
and younger children (,7 years
of age) with signiﬁcant acne vulgaris, evaluation for signs of sexual
precocity, virilization, and/or growth
abnormalities that may indicate an
underlying systemic abnormality
(endocrinologic diseases, tumors,
gonadal/ovarian pathology) and appropriate workup and/or referral to
a pediatric endocrinologist may be
warranted. (SOR: C).
Neonatal Acne
Infantile Acne
Neonatal acne is estimated to affect up
to 20% of newborns.9 The major controversy in this age group is whether
the lesions truly represent acne or one
of a number of heterogeneous papulopustular acneiform conditions typically without comedones, such as
neonatal cephalic pustulosis (NCP) or
transient neonatal pustular melanosis.
Although rare, some neonates may
present with androgen-driven comedonal and inﬂammatory acne.8,10 NCP
pustules are usually conﬁned to the
Infantile acne may begin at ∼6 weeks of
age and last for 6 to 12 months or,
rarely, for years. It is more common in
boys and presents with comedones as
well as inﬂammatory lesions, which
can include papules, pustules, or occasionally nodular lesions. Physical
examination should include assessment of growth including height,
weight, and growth curve; testicular
growth and breast development; presence of hirsutism or pubic hair; clitoromegaly; and increased muscle
mass.12 Should workup for a hormonal
anomaly be considered, a pediatric
endocrinology referral and/or bone
age and serologic evaluation of folliclestimulating hormone, luteinizing hormone,
testosterone, and dehydroepiandrosterone sulfate levels are recommended.
No further workup is necessary for the
majority of cases in the absence of
hormonal abnormalities. It is also important to distinguish true infantile
acne from other similar cutaneous
lesions, because there is some evidence
that infantile acne predisposes to more
severe adolescent acne.13 Infantile acne
may be treated with topical antimicrobial agents; topical retinoids; noncycline
antibiotics, such as erythromycin; and,
occasionally, isotretinoin, though all are
without FDA indication for use in this
age group.
Consensus Recommendation:
Most infantile acne is self-limited
and not associated with underlying
endocrine pathology. However, in
patients with additional physical
signs of hormonal abnormality,
a more extensive workup and/or
referral to a pediatric endocrinologist may be appropriate. (SOR: C).
Mid-Childhood Acne
Mid-childhood acne presents primarily
on the face with a mixture of comedones
and inﬂammatory lesions.10 Children
between the ages of 1 and 7 years,
however, do not normally produce
signiﬁcant levels of adrenal or gonadal
androgens; hence, acne in this age
group is rare. When it does occur, an
endocrine abnormality should be suspected. A workup by a pediatric endocrinologist is usually warranted to rule
out adrenal or gonadal/ovarian pathology including the presence of
androgen-secreting tumors. Increased
bone age and accelerated growth, as
evidenced by deviation from standardized age-appropriate growth curves,
are important indicators of the effects
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TABLE 3 Differential Diagnosis of Acne in
Younger Pediatric and Adolescent
Patients
Adolescent (∼12–18 y of age)
Corticosteroid-induced acne
Demodex folliculitis
Gram-negative folliculitis
Keratosis pilaris
Malassezia (pityrosporum) folliculitis
Papular sarcoidosis
Perioral dermatitis
Pseudofolliculitis barbae
Tinea faciei
Preadolescent ($7 to #12 y of age)
Acne venenata or pomade acne (from the use
of topical oil-based products)
Angioﬁbromas or adenoma sebaceum
Corticosteroid-induced acne
Flat warts
Keratosis pilaris
Milia
Molluscum contagiosum
Perioral dermatitis
Syringomas
Mid-Childhood (1–7 y of age)
Adrenal tumors
Congenital adrenal hyperplasia
Cushing syndrome
Gonadal tumors
Ovarian tumors
PCOS
Premature adrenarche
True precocious puberty
Any Age
Acne venenata or pomade acne (from the use of
topical or oil-based products)
Bilateral nevus comedonicus
Chlorinated aromatic hydrocarbons (chloracne)
Corticosteroids (topical, inhaled, and oral)
Demodicidosis
Facial angioﬁbromas (tuberous sclerosis)
Flat warts
Infections (bacterial, viral, and fungal)
Keratosis pilaris
Medication-Induced (anabolic steroids,
dactinomycin, gold, isoniazid, lithium, phenytoin,
and progestins)
Milia
Miliaria
Molluscum contagiosum
Perioriﬁcial dermatitis
Rosacea
Adapted from Tom and Friedlander6 and Krakowski and
Eichenﬁeld.7
of excess androgens. In addition to treatments to address androgen-secreting
tumors or congenital adrenal hyperplasia, the treatment of mid-childhood
acne is similar to that of adolescent
acne except that oral tetracyclines are
usually not an option in children younger
S166
than 8 years of age because of the risk
of damage to developing bones and
tooth enamel. Hormonal therapy could
be used if warranted by endocrinologic
pathology.8
Consensus Recommendation:
Mid-childhood acne is very uncommon and should warrant an endocrinologic workup for causes of
hyperandrogenism. (SOR: C).
Preadolescent Acne
It is not uncommon for acne vulgaris to
occur in preadolescents, as a result of
normal adrenarche and testicular/
ovarian maturation. Acne may be the
ﬁrst sign of pubertal maturation.8 In
fact, with the trend toward earlier age
of onset of adrenarche and menarche,
there appears to be a downward shift
in the age at which acne ﬁrst appears.
Preadolescent acne is characterized by
a predominance of comedones on the
forehead and central face (the socalled “T-zone”) with relatively few inﬂammatory lesions.10 Early presentation may include comedones of
the ear.
Consensus Recommendation:
Preadolescent (7–12 years) acne is
common and may precede other
signs of pubertal maturation. Workup
beyond history and physical is generally unnecessary unless there
are signs of androgen excess, PCOS,
or other systemic abnormalities.
(SOR: B).
PEDIATRIC ACNE CLASSIFICATION
AND SEVERITY ASSESSMENT
In general, treatment of pediatric acne
vulgaris is similar to acne treatment in
older adolescents and adults and is
based on acne pathophysiology. The
pathogenesis of acne involves the interplay of 4 factors: sebaceous hyperplasia under the inﬂuence of increased
androgen levels, alterations in follicular
growth and differentiation, colonization
of the follicle by Propionibacterium
acnes (P acnes), and consequent immune response and inﬂammation.15
History and physical examination are
the most important parts of the assessment in this age group. Further
workup is generally unnecessary unless there are signs of excess androgens.7 Polycystic ovary syndrome
(PCOS) or another endocrinologic abnormality may be considered when the
acne is unusually severe, accompanied
by signs of excess androgens, or is
unresponsive to treatment.14 Pelvic ultrasound is not considered useful for
diagnosis of PCOS because it is nonspeciﬁc.
A useful clinical categorization of acne
is based on predominate morphology:
comedonal with closed and open
comedones (“whiteheads” and “blackheads”); inﬂammatory, with erythematous papules, nodules, or cystlike
nodular lesions; or mixed, where both
types of lesions are present. The microcomedo is the not-clinically-apparent
precursor of both comedonal and inﬂammatory lesions. It is a product of hyperactive sebaceous glands and altered
follicular growth and differentiation.
Reduction in existing microcomedones
and prevention of the formation of new
ones is central to the management of
all acne lesions.16
Treatment of uncomplicated preadolescent acne is comparable to that
of acne in older age groups, as discussed later. It is important in this age
group to elicit the patient’s level of
concern regarding his or her acne,
which may not always be concordant
with parental concern.
Comedones form as a result of increased cell division and cohesiveness
of cells lining the follicular lumen. When
these cells accumulate abnormally, mix
with sebum, and partially obstruct the
follicular opening, they form a closed
comedo (whitehead). If the follicular
opening is larger, the keratin buildup is
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SUPPLEMENT ARTICLE
more visible and can darken to form an
open comedo (blackhead). Follicular
colonization with P acnes leads to inﬂammation via the production of inﬂammatory mediators and the formation of
inﬂammatory papules and pustules.
Nodular acne is characterized by a
predominance of large inﬂammatory
nodules or pseudocysts and is often
accompanied by scarring or the presence of sinus tracts when adjacent
nodules coalesce.
Acne severity may be classiﬁed clinically as mild, moderate, or severe based
on the number and type of lesions and
the amount of skin involved. Although
there are numerous grading systems by
which to deﬁne acne severity, there is no
agreed-upon standard, and interpretation is subjective. Many grading systems are most useful for research
purposes. For clinical purposes, simplicity is key. Typically, patients’ assessments do not correlate well with
either those of physicians or published
severity scales.17 The panel noted that
severity scales frequently overemphasize
inﬂammatory lesions. For example, in
some research settings, a patient
might be classiﬁed as having mild
acne because he or she has only a few
inﬂammatory lesions in the presence
of hundreds of closed comedones. In
such cases, the patient (and the physician) is more likely to consider his
or her acne to be severe. Determination of severity can be modiﬁed by
extent of involvement and scarring as
well.
Although some acne may resolve without residual changes, inﬂammatory
acne may result in the formation of
signiﬁcant scars. In darker skin, postinﬂammatory hyperpigmentation (PIH)
is common. Residual erythema can occur as well. These changes are most
often reversible but can take many
months to fully resolve. Recognizing
these as secondary changes is important when determining the efﬁcacy of
treatment as patients may not recognize the improvement or think they
have scarring. Effective and early
treatment is essential to prevent
scarring as well as postinﬂammatory
changes and to limit the long-term
physical and psychological impact of
acne.
It has been repeatedly demonstrated
that acne can have a signiﬁcant adverse
impact on quality of life, and that the
level of distress may not correlate directly with acne severity.18,19 In 1 study,
assessments using several quality of
life instruments revealed deﬁcits for
acne patients who did not correlate
with clinical assessments of severity.20
Reported social, psychological, and
emotional symptoms were as severe as
those reported by individuals with
chronic medical conditions such as
chronic asthma, epilepsy, diabetes, and
back pain or arthritis. Adolescents, in
particular, may be insecure about their
appearance and vulnerable to peer
opinions. Because social functioning
and quality-of-life decrements may not
correlate with disease severity, even
mild acne may be more troubling to
young patients than they are willing to
admit.21
Consensus Recommendation:
Acne can be categorized as predominately comedonal, inﬂammatory, and/or mixed. Presence or
absence of scarring, PIH, or erythema should be assessed. Severity may be broadly categorized as
mild, moderate, or severe. (SOR: A).
APPROACH TO PEDIATRIC ACNE
THERAPY
The therapeutic objectives in acne are
to treat as many age-appropriate
pathogenic factors as possible by reducing sebum production, preventing
the formation of microcomedones,
suppressing P acnes, and reducing inﬂammation to prevent scarring.
Although no single acne treatment,
apart from isotretinoin, addresses all 4
pathogenic factors, it is now clear that
many of the medications traditionally
used to treat acne actually act by more
than 1 mechanism. In addition to targeting the largest number of pathogenic factors, the approach to pediatric
acne should be to use the least aggressive regimen that is effective while
avoiding regimens that encourage the
development of bacterial resistance.
Educating a patient (and parents) about
reasonable expectations of results and
discussing management of treatmentrelated side effects can maximize
both compliance and efﬁcacy.
Numerous medications are available to
treat acne. Design of an effective regimen is facilitated by an increased understanding of the mechanisms of
action, the side effect proﬁle, and the
indications and contraindications of
key antiacne agents discussed later.
OVER-THE-COUNTER TREATMENT
OPTIONS
Nationwide television commercials and
magazine ads abound with over-thecounter (OTC) products. Although largely
untested in controlled clinical trials,
many of these products are considered
somewhat effective, particularly for
patients with mild acne. Those which
have been tested include salicylic acidcontaining topical products and many
benzoyl peroxide (BP) products described in further detail later. Salicylic
acid has revealed some efﬁcacy in acne
trials, although when tested head-tohead with other topicals, particularly BP,
it is generally less effective.22,23 Nonprescription, nonbenzoyl-peroxide-containing
products appear to be somewhat effective for the treatment of acne, especially mild acne, though there is limited
published evidence supporting their
efﬁcacy in the treatment of acne.
Sulfur, sodium sulfacetamide, and
resorcinol are active ingredients in
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several OTC dermatology niche products. Sulfur exhibits mild antibacterial
and keratolytic properties.24 Because
of sulfur’s distinctive odor, it is often
combined with sodium sulfacetamide
to mask the scent.25 It is often used in
adult female acne because of its favorable tolerability.26,27 Resorcinol also
has mild antimicrobial properties and
is typically formulated in a 2% concentration in combination with 5%
sulfur.
One common acne myth is that poor
hygiene and improper cleansing cause
acne.21,28 The role of facial cleansing in
acne is to remove makeup, dirt, and
excess oil.29 Use of the wrong, too
harsh cleanser can disrupt skin barrier, increase transepidermal water
loss, encourage bacterial colonization, promote comedones, and cause
symptoms of burning and stinging.30,31
Typically, twice-daily washing with a
gentle soap-free, pH-balanced cleanser
is recommended. Antibacterial washes,
other than BP, have not been shown to
be useful in the treatment of acne.
Facial toners can decrease oiliness and
remove makeup and traces of dirt. They
are a common component of several
prepackaged combination acne treatment regimens. Patients should be cautious not to overuse facial toners
becausetheycanbeirritating.Ifirritation
occurs, this will adversely affect the
tolerability of acne medications.
Another common acne myth is that use
of cosmetics worsens acne. On the
contrary, use of concealing oil-free,
noncomedogenic makeup can improve patient quality of life and does not
worsen the severity of acne.32,33 Use of
cosmetics in patients with acne has not
been shown to delay treatment response either.
BP has been shown to be the most
widely studied of OTC products and has
shown to be one of the most versatile,
safe, inexpensive, and effective acne
therapies.34,35 Its lipophilic nature perS168
mits it to penetrate the stratum corneum and enter the pilosebaceous unit
where P acnes resides. It acts via the
generation of free radicals that oxidize proteins in the P acnes cell wall.
It also has been shown to have mild
comedolytic36 and antiinﬂammatory
properties.37,38 BP helps limit the development of P acnes resistance to
antibiotics and also provides increased
efﬁcacy in combination with retinoids.39,40
So far, antibiotic resistance to BP has
not been reported.41–44
Although issues regarding genotoxicity
have been raised in the past, BP has now
been labeled as “GRASE” (generally
regarded as safe and effective) by the
FDA, and all topical monotherapy
products have been made available OTC
since 2011. Labeling includes advice to
avoid the eyes, lips, and mouth. The
product can cause bleaching of hair
and clothing, and risk of increased
sunburn and the need for photoprotection also are mentioned. BP frequently causes dryness, erythema, and
peeling upon initiation of treatment.
Starting with lower concentrations (eg,
2.5%) and utilizing more emollient
vehicles if needed can help alleviate
these discomforts. Allergic contact
dermatitis to BP occurs in 1 in 500
people and should be considered if
a patient complains of itching and
swelling of the eyes.
BP is available in a variety of formulations and in concentrations ranging from 2.5% to 10%. There is some
evidence that higher concentrations do
not increase efﬁcacy but are more irritating. However, the back may be
a “special site” circumstance, where
increasing concentration or prolonged
contact leads to increased efﬁcacy.45
Formulations include a variety of topical leave-on preparations as well as
washes that permit patients to remove
BP from the skin, reducing the possibility of bleaching of clothing, bedding,
or towels.38 It has been suggested that
short-contact BP therapies do not signiﬁcantly reduce bacterial load, but data
are lacking. However, they can be effective if left on the skin for the duration
recommended by the manufacturer.
Consensus Recommendations:
BP is generally regarded as a safe
and effective medication that may
be used as monotherapy or in topical combination products for mild
acne or in regimens of care for
acne of all types and severities.
(SOR: A).
BP may minimize development of
antibiotic-resistant P acnes when
used with topical or systemic antibiotics. (SOR: C).
PRESCRIPTION TREATMENT
OPTIONS: SINGLE AGENTS
Topical Retinoids
Topical retinoids, as monotherapy and
in topical combination products, are
used routinely for the treatment of acne
vulgaris. Their safety and efﬁcacy are
well documented in large pivotal trials
that included pediatric patients ranging
from 12 to 18 years of age. Subsequently, because acne routinely
presents in patients younger than 12
years of age, topical retinoids are
widely used off-label in this age group.
Tretinoin gel 0.05% (Atralin, Coria Laboratories, Fort Worth, TX) is FDAapproved for use in children $10 years of
age,46 and adapalene and benzoyl peroxide gel 0.1%/2.5% (Epiduo, Galderma
Laboratories, LP, Fort Worth, TX) is indicated for ages 9 and older. Adapalene
gel, tretinoin gel, and tretinoin microsphere gel have been investigated in
both open-label and blinded studies in
children under 12 years of age.47–49
Retinoids normalize desquamation of
the follicular epithelium, thus preventing
the formation of new microcomedones,
precursors to both comedonal and inﬂammatory lesions, and also promote
the clearing of existing microcomedones.50
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In addition, some topical retinoids
also have direct antiinﬂammatory
activity.43,51,52 At present, 3 topical
retinoids (tretinoin, adapalene, and
tazarotene) are available by prescription in the United States. Each is
available in a variety of formulations
and concentrations (Table 4).53 Their
most common adverse effects include
burning, stinging, dryness, and scaling.15 These effects may be reduced by
initiating treatment with the lowest
strength, typically sufﬁcient to treat
mild acne, or by recommending regular
use of a moisturizer. Patients should be
instructed not to spot-treat but rather to
use a pea-size amount to cover the entire face. In patients with sensitive skin,
therapy can be initiated with thriceweekly application, increasing to daily
use as tolerated.48
Tolerability may be further improved by
the use of a noncomedogenic moisturizer that includes a sunscreen.15,38 Topical tretinoin was the ﬁrst retinoid
approved for use in the United States. It
is available in a variety of vehicles such
as a micronized gel or a polymerized
cream for increased tolerability. In a
12-week open-label study of 40 patients
with mild/moderate acne ages 8 to 12
years (mean age, 10.7 years), tretinoin
microsphere gel 0.04% produced a signiﬁcant decrease in Evaluator’s Global
Severity Score (P , .001) from baseline
to week 12, with 75% of participants
graded as almost clear or mild. Skin
irritation occurred in 35% of the
patients but was mild in most cases and
improved by study’s end.48
Other topical retinoid alternatives
to tretinoin include adapalene and
tazarotene. Adapalene, a distinct retinoid that is generally well tolerated, is
available in cream, gel, and lotion
formulations.53,54 Adapalene is photostable, including in ﬁxed-combination
with BP.55
Although studies regarding the use of
topical retinoids in pediatric patients
TABLE 4 Formulations and Concentrations of Topical Retinoids
Retinoid
Tretinoin
Adapalene
Tazarotene
Formulationa
Strength, %
Pregnancy Category
Cream
Gel
Gel (micronized)
Microsphere gel
Polymerized cream
Polymerized gel
Cream
Gel
Solution
Lotion
Gel
Cream
0.025, 0.05, 0.1
0.01, 0.025
0.05
0.04, 0.1
0.025
0.025
0.1
0.1, 0.3
0.1
0.1
0.05, 0.1
0.05, 0.1
C
C
X
Adapted from Imahiyerobo-Ip and Dinulos.52
a Numerous generic retinoids are available. Branded products are available under the following trade names: Atralin, Avita,
and Retin-A Micro for tretinoin; Differin for adapalene; and Tazorac for tazarotene.
are extremely rare in the literature, in
a 16-week study of 12 infants with infantile acne (mean age, 12.6 months),
0.1% adapalene cleared both comedonal and inﬂammatory lesions in
a median of 3.4 months with side effects
that did not require discontinuation,
underscoring the reported high tolerability of adapalene.47 Tazarotene is an
effective topical retinoid, but it is used
less often as a ﬁrst-line agent for acne
because of concerns regarding tolerability; it is also known to be more irritating.56
In the absence of signiﬁcant systemic
absorption of the active ingredients, the
possibility of intolerability remains the
primary safety issue. However, older
girls who may be of childbearing potential are often of the age group
treated with topical retinoids. Naturally
circulating endogenous retinoids are
present in the plasma of normal healthy
girls as a result of dietary consumption
of foods such as ﬁsh, carrots, sweet
potatoes, and red peppers. Continuous
daily dosing of tretinoin 0.1% cream,
tazarotene 0.1% gel, and adapalene
0.1% gel has been shown to only slightly
increase the mean maximum plasma
levels of circulating retinoids in most
patients. In 1 study, serum retinoid
levels were found to be more heavily
inﬂuenced by dietary intake than by
topical application of tretinoin. In
a study of 215 women accidentally exposed to topical tretinoin during the
ﬁrst trimester of pregnancy, Jick et al57
showed no difference in developmental
anomalies compared with 430 agematched controls. Tretinoin and adapalene have a pregnancy category C
and tazarotene a category X rating.
Consensus Recommendation:
Topical retinoids (tretinoin, adapalene, tazarotene) may be used as
monotherapy or in combination
products and in regimens of care
for all types and severities of acne
in children and adolescents of all
ages. (SOR adolescents: A; SOR preadolescents and younger: B).
Antibiotics/Antimicrobials
Although acne is not an infection,
antibiotics reduce P acnes colonization
of the skin and follicles. They are effective in acne both by inhibiting bacterial protein synthesis38 and by
decreasing inﬂammation via inhibition
of bacterial proinﬂammatory mediators and decreasing neutrophil chemotaxis.58,59
The alarming increase in P acnes resistance to both topical and systemic
antibiotics used to treat acne not only
renders these drugs less effective
against acne but may also inﬂuence
commensal bacteria in both the acne
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patient and his or her environment.60
Resistance may occur with both appropriate and incorrect use of antibiotics.58
Oral Antibiotics
(administered as 1 tablet daily) is FDA
approved for the treatment of moderate to severe inﬂammatory acne vulgaris that is not predominantly nodular
in patients $12 years of age.62 Both
immediate-release doxycycline and
immediate-release minocycline have
listed the indication in their FDAapproved labeling of adjunctive use
for severe acne, although this was not
based on formal submission for FDA
approval for either drug.63,64 The commonly used oral antibiotics for children
older than 8 years are tetracycline
derivatives, including tetracycline,
doxycycline, and minocycline. Although
erythromycin was used successfully in
the past, the worldwide prevalence of
P acnes resistance to erythromycin
has led to decreased use of this agent,
both orally and topically, for acne.60,65,66
Comparative studies are limited, but
the second-generation tetracyclines,
doxycycline and minocycline, are preferred because of pharmacokinetic
advantages allowing for once-daily
administration in most cases, greater
lipophilicity that is believed to augment
follicular penetration, and lower prevalence of resistant P acnes strains as
compared with tetracycline.15,67,68 For
children under 8 years of age and
those with tetracycline allergies, alternative oral antibiotic agents, including erythromycin, azithromycin,
and trimethoprim/sulfamethoxazole,
should be used very judiciously because of the potential risk for severe
adverse reactions, such as toxic epidermal necrolysi.69–72 Table 5 summarizes the dosages, adverse events,
and precautions regarding the use of
the most frequently used oral antibiotics for treatment of inﬂammatory
acne.69
Interestingly, with the exception of
extended-release minocycline, use of
oral antibiotics in acne is not FDA approved.61 Extended-release minocycline dosed at 1 mg/kg per day
The panel agreed that education and
monitoring related to potential adverse
events is important with oral antibiotic
therapy for acne. Photosensitivity (phototoxicity) and “pill esophagitis” are
Topical Antibiotics
Topical antibiotic monotherapy is not
recommended because of both its slow
onset of action and the greater likelihood of the development of bacterial
resistance. If topical or oral antibiotic
treatment is to be prolonged more than
a few weeks (as is usually the case in
acne treatment), topical BP should be
added to optimize efﬁcacy via its nonspeciﬁc antimicrobial activity and reduce the emergence of less sensitive
P acnes variants.60 It has even been
suggested that, if antibiotic therapy is
maintained for more than 3 months,
a BP washout should occur between
courses, although no large studies
have addressed this recommendation.15
Use of topical antibiotics in ﬁxedcombination products containing BP
may help reduce the emergence of
antibiotic-resistant strains of bacteria.
In the case of the ﬁxed-combination of
tretinoin and clindamycin, concomitant
use of BP is recommended.
Consensus Recommendation:
Topical antibiotics (clindamycin,
erythromycin) are not recommended as monotherapy because of
slow onset of action and predictable
emergence of antibiotic-resistant
bacterial organisms. (SOR: C). If
topical antibiotic treatment is to
be prolonged for more than a few
weeks, topical BP should be added,
or used in combination products.
(SOR: C).
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most common with oral doxycycline.73–75
The former can be circumvented with
appropriate photoprotection, and the
latter by ingestion with a large glass
of water, maintaining an upright position for at least 1 hour after ingestion,
and use of an enteric-coated formulation.76 Although rare, drug hypersensitivity syndrome (DHS), Stevens-Johnson
syndrome, or lupuslike syndrome (LLS)
may occur with administration of
minocycline. DHS presents early after
initiation of minocycline therapy, usually within the ﬁrst 2 to 8 weeks,
commonly with ﬂulike symptoms (ie,
fever, malaise), diffuse exanthemlike
erythema, facial edema, cervical lymphadenopathy, and elevated hepatic enzymes (especially transaminases),
although other organs may be involved with interstitial inﬂammation
(eg, pneumonitis, nephritis, and thyroiditis).77,78
Minocycline-associated LLS, which is
commonly reversible, generally develops after chronic exposure (ie, many
months to years), and often presents
with malaise, distal polyarthralgias
with or without polyarthritis, and, more
rarely, autoimmune hepatitis.78–80 Most
cases of minocycline-associated LLS do
not have skin eruptions, although rare
reports have revealed superﬁcial vasculitis such as cutaneous polyarteritis
nodosa. A positive antinuclear antibody
test is often present, although not always
diagnostic or predictive of minocycline
LLS, along with other autoantibodies.
The autoantibody proﬁle may be highly
variable among cases of minocyclineassociated LLS. When present, p-anca
positivity is believed to strongly support the diagnosis. Presence of antihistone antibody is not required to
conﬁrm the diagnosis of LLS and may
not be detected in some cases. Finally,
within the ﬁrst few weeks of minocycline treatment, physicians should consider the rare risk of serumsicknesslike
reaction.78 Cutaneous and/or mucosal
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TABLE 5 Oral Antibiotics Used for Treatment of Moderate-to-Severe Acne Vulgaris
Antibiotic
Recommended Dosage
a
Doxycycline
50–100 mg QD or BID;
150 mg QD
Erythromycinb
250–500 mg QD-BID
Tetracycline
500 mg BID
Minocycline (immediate release)
50–100 mg QD-BID
Minocycline extended-release tablets
(available since 2006)
1 mg/kg QD
Potential Adverse Effects
Comments
Gastrointestinal upset especially pill
Can be taken with meals, take with large glass
esophagitis (reduced with enteric coated
of water and maintain upright position $1 h
formulation); photosensitivity (especially in
to decrease risk of esophagitis; optimize
doses of $100 mg daily); staining of
photoprotection especially in sunny season
forming tooth enamel (if given #8 y of age);
or with known increased outdoor exposure;
vaginal candidiasis; BIH (rare).
avoid in children who have not developed
set of permanent teeth; monitor for blurred
vision, severe headaches sometimes with
nausea and/or vomiting.
Gastrointestinal upset; drug-drug interactions High prevalence of antibiotic-resistant P acnes.
such as increase in carbamazepine serum
levels → toxicity.
Fixed drug eruption; gastrointestinal
Ingest on empty stomach preferable;
symptoms; staining of forming tooth enamel
absorption is decreased if taken with iron,
(if given #8 y of age); vaginal candidiasis;
calcium, or many other metal ions found in
BIH (rare).
vitamins/supplements, dairy products
(including milk, yogurt); avoid in children
who have not developed set of permanent
teeth; avoid in renal or hepatic disease;
monitor for blurred vision, severe
headaches sometimes with nausea and/or
vomiting.
Cutaneous and/or mucosal hyperpigmentation Can be taken with meals; warn patient about
dizziness/vertigo (suggest initial doses be
of skin and mucosal sites (oral, sclera,
given when at home and not driving to
conjunctiva); bone may be affected in some
assess if patient susceptible to these
cases; DHS (systemic) often with hepatitis
effects); avoid in children who have not
and/or pneumonitis (most often will occur
developed set of permanent teeth; monitor
within the ﬁrst 1–2 mo); hepatitis
for malaise, ﬂulike symptoms, diffuse
(hypersensitivity [tends to occur more
erythema with facial swelling, respiratory
acutely early in treatment course] or
complaints suggestive of drug
autoimmune [more often to occur with
hypersensitivity especially within the ﬁrst
more chronic use of several months to
few months after starting therapy;
years]); LLS; Stephens-Johnson syndrome;
discontinue therapy if this side effect
vestibular toxicity (tends to occur within the
suspected; monitor for malaise, distal
ﬁrst few days after starting therapy);
arthralgias with or without arthritis
staining of forming tooth enamel (if given
especially with more prolonged use of
#8 y of age); vaginal candidiasis; BIH (rare).
several months to years suggestive of LLS;
monitor for pigmentary changes on skin
especially face, trunk, legs, and scars;
monitor for blue or gray discoloration of
sclera, oral mucosa, nail beds; monitor for
blue discoloration of acne scars; some cases
maybe persistent even with discontinuation;
monitor for blurred vision, severe
headaches sometimes with nausea and/or
vomiting.
Same potential reactions as above although Same as above except lower incidence of acute
vestibular side effects with weight-based
above side effects reported predominantly
dosing (1 mg/kg per day); not yet known if
with immediate-release formulations
(available since 1971); lower incidence of
other potential side effects reduced with
acute vestibular side effects with weightweight-based dosing of the extendedrelease formulation; less accumulation of
based dosing (1 mg/kg per day).
minocycline over time due to
pharmacokinetic properties of extendedrelease formulation; may possibly correlate
with decreased risk of cutaneous or
mucosal hyperpigmentation if dosed
properly by patient weight.
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TABLE 5 Continued
Antibiotic
Trimethoprim/ sulfamethoxazole
Recommended Dosage
160–800 mg BID
Potential Adverse Effects
Comments
Severe cutaneous eruptions (toxic epidermal Not generally recommended for use as ﬁrst or
necrolysis, Stevens-Johnson syndrome);
second-line agent for acne; to be used
bone marrow suppression (anemias,
judiciously in selected refractory cases;
neutropenia, and thrombocytopenia);
obtain complete blood cell count at baseline
hypersensitivity reactions; drug eruptions
and periodically thereafter; additional
(rash); ﬁxed drug eruption.
caution in patients with history of anemia
(megaloblastic types); may warrant
hematologic consultation if use of this agent
highly considered.
BID, twice daily; QD, once daily. Adapted from Tan,69 Gollnick et al,15 and Del Rosso and Kim.70
a Enteric-coated and double-scored 150 mg tablet available; double-scored tablet provides 50 mg/unit (tablet can be administered whole or broken into total of 3 segments).
b Use of lower dose for maintenance therapy based on anecdotal experience or clinical impression and not by large-scale clinical trials.
hyperpigmentation may occur in some
patients treated with minocycline and
appears to correlate with cumulative
drug exposure over time in most
cases reported with use of immediaterelease minocycline formulations available since 1971.81–83 Weight-based
dosing of minocycline (1 mg/kg per
day) using the extended-release tablet
formulation once daily, available since
mid-2006, may potentially reduce the
risk of hyperpigmentation as both the
peak serum level and total drug exposure are diminished as compared
with immediate-release minocycline
formulations; however, continued pharmacosurveillance is warranted to conﬁrm this preliminary observation.84
Face, trunk, legs, oral mucosa, sclera,
and nail beds should be examined periodically.
Acute vestibular adverse events (ie,
vertigo, dizziness) that sometimes
occur in patients treated with minocycline develop early after initiation of
treatment and are reversible with
discontinuation of therapy.85–87 Weightbased dosing of extended releaseminocycline (1 mg/kg once daily) has
been reported to reduce the risk for
development of acute vestibular adverse events as compared with a daily
dose up to threefold higher.61
A rare central nervous system-related
side effect associated with use of tetracycline, doxycycline, or minocycline is
benign intracranial hypertension (BIH),
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also referred to as pseudotumor cerebri.
A high index of suspicion is warranted
if headache and visual disturbances,
sometimes accompanied by nausea
and/or vomiting, are noted to detect BIH
early because persistence can lead to
severe loss of vision, which may be
permanent.88
Second-generation tetracyclines
In the past 20 years, P acnes has become less sensitive to oral and topical antibiotics because of increasing
selection pressure arising from their
widespread usage.60,66,70,89 However,
strategies listed in Table 6 can minimize the potential for the development of resistance to antibiotics
when used to treat acne, especially as
the duration of therapy is often prolonged over months. Recent studies
have revealed that the use of systemic antibiotics for acne treatment
also may be associated with an increase in resistant coagulase-negative
staphylococci and a possible increased risk of upper respiratory
tract infection; however, further
studies are needed to evaluate the
true clinical implications of these potential risks.60,90
Patients should be educated and
Consensus Recommendations:
Oral antibiotics are appropriate
for moderate-to-severe inﬂammatory acne vulgaris at any age. Tetracycline derivatives (tetracycline,
doxycycline, and minocycline) should
not be used in children younger than
8 years of age. (SOR: B).
(doxycycline, minocycline) are sometimes preferred to tetracycline because of ease of use, fewer problems
with absorption with food and minerals in vitamins and other supplements, and less-frequent dosing.
(SOR: C).
monitored for potential adverse
events when utilizing oral antibiotics for acne. (SOR: B).
Topical Dapsone
Dapsone, a synthetic sulfone, has antimicrobial and antiinﬂammatory effects;
however, its activity in the treatment
TABLE 6 Strategies to Optimize Oral
Antibiotic Therapy in Acne Vulgaris
Use in moderate or severe inﬂammatory acne
vulgaris in combination with a topical regimen
that includes BP.
Avoid antibiotic monotherapy when using either an
oral or topical antibiotic agent for acne vulgaris.
Discontinue (or taper) within 1 to 2 mo once new
inﬂammatory acne lesions have stopped
emerging.
Incorporate a topical retinoid into the regimen
early to augment overall therapeutic beneﬁt and
prepare for discontinuation of oral agent with
goal of maintaining control with topical
program; may also use BP-containing
formulation with topical retinoid for
maintenance of control of acne.
If retreatment is needed, use the same oral
antibiotic that was previously effective in the
past.
Adapted from Gollnick et al,15 Leyden,50 and Del Rosso and
Kim.70
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SUPPLEMENT ARTICLE
of acne as a topical agent is not believed
to be related to P acnes reduction.91
Recently, a 5% dapsone gel was approved in the United States for acne
treatment. It was evaluated in two 12week randomized, double-blind, phase
3 trials in patients aged 12 and older
with mild, moderate, or severe acne.92
The 3010 subjects used dapsone 5%
gel twice daily or vehicle gel. A combined analysis revealed a statistically
signiﬁcant reduction in noninﬂammatory and inﬂammatory lesions by
week 12 compared with vehicle (P ,
.001). Treatment response was rapid,
with statistically signiﬁcant intergroup differences in lesion count at
4 weeks. Adverse events were comparable between dapsone gel and
vehicle gel and rarely led to discontinuation.
Available studies demonstrate that
topical dapsone is most effective
against inﬂammatory lesions, with efﬁcacy enhanced more when combined
with a topical retinoid as compared
with BP.92,93 The safety of 5% dapsone
gel applied twice daily has been demonstrated in patients who are glucose
6 phosphate dehydrogenase-deﬁcient
and in patients who are sulfonamide
allergic.94–96 The most common applicationsite reactions consisted of erythema
and dryness that were similar between groups. A temporary orange
staining of the skin can occur when
BP and topical dapsone are used
together.
tretinoin use in acne treatment of
adolescents and preadolescents and
agrees that it may be used in younger
patients with severe, refractory, and
scarring acne.
Its most common side effects include
dry, chapped skin and lips, dry eyes, and
myalgias. Nose bleeds secondary to
dryness also are common. These effects
are generally reversible upon discontinuation of the drug. Some patients
may experience increases in serum
triglycerides and changes in liver
enzymes. Both fasting serum lipids and
liver function tests should be obtained
at baseline and monitored periodically
thereafter. A major adverse effect of
isotretinoin and a public health concern
is its teratogenic potential. For this
reason, the FDA mandated in 2007 the
implementation of a computerized risk
management program (iPledge), which
registers all isotretinoin patients, physicians, pharmacies, and manufacturers and ensures monthly monitoring
of pregnancy status in females of
childbearing potential.
Three of the most signiﬁcant and controversial groups of adverse effects
attributed to isotretinoin and described in the drug’s package insert
are skeletal issues; potential for development of inﬂammatory bowel
disease (IBD); and mood changes, depression, suicidal ideation, and suicide, which are addressed in greater
detail because of their relevance in
pediatric patients.98
Oral Isotretinoin in Severe Acne
Bone Effects
Oral isotretinoin targets all of the
pathophysiologic factors involved in
acne typically producing excellent
results.15 A recent consensus conference on its use recommends
a starting dose of 0.5 mg/kg per day
for the ﬁrst 4 weeks to avoid initial
ﬂares, increasing to the full dosage of
1 mg/kg per day.97 The panel concurs
with this recommendation for iso-
The interaction between retinoids and
skeletal homeostasis is complex. Animal studies have indicated that excessive intake of retinoids can have
inhibitory effects on both osteoblast
and osteoclast activity that may pose
a theoretical risk for fractures or hyperostosis.99–112 Well-designed clinical
studies involving human subjects have
generated conﬂicting data on the as-
sociation between excessive intake of
vitamin A with the incidence of fractures. In evaluating isotretinoin speciﬁcally, 1 small prospective cohort
study associated isotretinoin with
minimal-to-mild bone demineralization
at speciﬁc sites (such as Ward’s triangle of the femur), but revealed that
these effects may be reversible.113 Additional data from small prospective
cohort114 and case control studies115,116
have, however, documented no measurable changes in bone mineralization
markers. These changes were not associated with increased risk of fractures in those treated with isotretinoin
at the standard doses and durations
used for acne.
Hyperostoses are thought to occur with
somewhat greater frequency among
those who received long-term systemic
retinoid therapy for disorders of keratinization. Hyperostosis during retinoid
use has been most strongly associated
with long-term therapy or chemoprevention, appears to be dose- and
duration-dependent, is often asymptomatic, and may resolve spontaneously. Overall, this phenomenon
appears to be uncommon among those
receiving isotretinoin for acne vulgaris.
Premature epiphyseal closure in association with retinoid therapy appears
to be a rare event and may occur in an
asymmetric or generalized fashion.
Only a single case has been reported in
association with isotretinoin administered for acne.117 Other cases have
primarily been reported as a consequence of isotretinoin therapy for
disorders of keratinization118 or neuroblastoma.113,119
IBD
There are conﬂicting data on the potential association between isotretinoin
and IBD. In available published reports,
21 patients with preexisting IBD who
subsequently receive isotretinoin have
been reported to tolerate the drug;
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S173
4 experienced worsening of IBD symptoms during therapy, suggesting that
the majority of patients with IBD who
received isotretinoin have largely tolerated isotretinoin for acne.107,120–128
The occurrence of IBD after exposure to
isotretinoin has been reported. These
are composed of case reports or small
case series (N = 18); a systematic review of FDA MedWatch Data129 highlighting 85 identiﬁed cases, of which 62
were deemed highly probable or
probable; and 1 large case-control
study involving 8189 cases of IBD,
which included 24 cases that had received isotretinoin.130 In this casecontrol study, only ulcerative colitis
was associated with previous isotretinoin use, and increasing cumulative dose or duration to isotretinoin
was associated with an elevated risk of
ulcerative colitis (1.5 odds ratio increase per 20 mg increase in dose, and
5.63 overall increased odds ratio in
association with longer duration).
At the same time, a case-control study
evaluating a Manitoba IBD Epidemiology
Database revealed no evidence for an
association between IBD and isotretinoin use131; in addition, a systematic literature-based search of case
reports, case series, and clinical trials
likewise revealed no evidence for an
association.132
An association between IBD (in particular, ulcerative colitis) and isotretinoin,
therefore, may potentially exist, although if it does, it appears to affect
a small subset of patients. The phenomenon appears to be rare, seems to
be idiosyncratic, and, at present, there
are no identiﬁable clinical characteristics that can currently a priori predict
this type of response. The association is
also fraught with confounding factors,
since the highest age of IBD onset
overlaps the age when patients develop
severe acne and when isotretinoin is
typically used. In addition, it was noted in
a study by Margolis et al114 that the maS174
jority of patients prescribed isotretinoin
treatment have been on extended antibiotic therapy and that previous antibiotic use may be an important
confounding variable in the relationship between IBD and isotretinoin.
Furthermore, a potential link between
IBD and inﬂammatory acne itself cannot be excluded.
Mood Disorders
The evidence regarding an association
between isotretinoin use and mood
disorders is primarily anecdotal, with
the original case series of 24 patients
reported by Hazen comprising the
reported experience on this linkage.
One open-label study compared acne
patients recalcitrant to antibiotics to
those receiving isotretinoin, and identiﬁed changes in brain metabolism in
the orbitofrontal cortex, which are
thought to partially mediate depressive
symptoms.133 However, the numbers of
patients studied were small (N = 28),
and those receiving isotretinoin had
more severe acne, which could correlate with more severe depressive
symptoms independent of the isotretinoin. Indeed, in a large crosssectional questionnaire-based study
of 3775 adolescents between 18 and 19
years of age who suffered from acne,
those with more severe acne were
more than twice as likely to have
mental health issues and 1.8 times
more likely to have suicidal ideation. In
fact, ∼1 in 4 adolescents with signiﬁcant acne were noted to have mental
health issues. A systematic review by
Marqueling and Zane134 identiﬁed 6
prospective studies and 3 retrospective studies that involved at least 20
patients, studied depressive symptoms
in human subjects as primary data,
and used epidemiologic techniques. In
this analysis, there was no apparent
increase in depression diagnoses or
symptoms when baseline was compared with after treatment with isotretinoin. Four subsequent additional
studies (2 prospective, 1 case-control,
and 1 cohort study) evaluated isotretinoin use and depressive symptoms.135,136 Although none of these
additional studies identiﬁed a positive
association between isotretinoin use
and depression, 2 of them indicated
that as acne improved, quality of life
improved137 and depressive symptoms and suicidal ideation actually
decreased.138
In summary, case reports and case
series have identiﬁed patients who
developed depressive symptoms while
receiving or after isotretinoin therapy,
and 1 study utilizing positron emission
tomography has documented changes
in cerebral metabolism in patients receiving isotretinoin therapy. Epidemiologic studies, however, do not currently
support a causative association between isotretinoin and depression, and
acne severity itself is a predictor of
mental health issues and suicidal ideation. Ongoing vigilance and surveillance of patients for mood changes
while on isotretinoin therapy seem
reasonable, but the data appear reassuring.
Consensus Recommendation:
Isotretinoin is recommended for
severe, scarring, and/or refractory
acne in adolescents and may be
used in younger patients. (SOR
adolescents: A; SOR preadolescents
and younger: C). Extensive counseling, particularly regarding the
avoidance of pregnancy as well
as careful monitoring of potential
side effects and toxicities, is recommended.
PRESCRIPTION TREATMENT
OPTIONS: TOPICAL FIXED-DOSE
COMBINATION THERAPIES
Numerous topical ﬁxed-dose combination products, including BP/clindamycin,
BP/adapalene, BP/erythromycin, and
tretinoin/clindamycin, are currently FDA
approved for pediatric patients 12 years
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SUPPLEMENT ARTICLE
and older as outlined in Table 7. All of the
products are pregnancy category C.
In the phase 3 pivotal trials for BP 2.5%/
clindamycin 1.2% gel (Acanya, Coria
Laboratories), 62% of enrolled patients
were between the ages of 12 and 17. In
a subanalysis of 12- to 17-year-old
patients, lesion count and success
rate were similar to those obtained in
the study as a whole.139 In the pivotal
trial for tretinoin 0.025%/clindamycin
1.2% (Ziana Gel, Medicis Pharmaceutical Corporation, Scottsdale, AZ), 51% of
enrolled patients were 12 to 17 years of
age and, in an unpublished subanalysis
for the pediatric age group, was essentially no different from the study
group as a whole. In the BP 2.5%/
adapalene 0.1% gel (Epiduo Gel,
Galderma Laboratories, LP, Fort Worth,
TX) pivotal trial, the mean age was 16.2
years and a subanalysis of results in
the 12- to 17-year-old group was similar to the study group as a whole.140
Although sometimes more costly than
single agents prescribed separately,
ﬁxed combinations applied once daily
are very convenient and thus may improve adherence.52,141
Consensus Recommendation:
Fixed-dose combination topical therapies may be useful in regimens of
care for all types and severities of
acne. (SOR adolescents: A; preadolescents and younger: B).
HORMONAL THERAPY
Hormonal therapy in acne is directed at
suppressing ovarian androgen pro-
duction and blocking the effects of
androgens on the sebaceous gland that
leads to reduction of sebum production
and improvement in acne. Combination
oral contraceptives (OCs; estrogen plus
progestin) block the ovarian production
of androgen, and antiandrogens, such
as spironolactone, block the effects of
androgens on the sebaceous gland. In
patients diagnosed with congenital
adrenal hyperplasia, low-dose glucocorticoids are used to suppress the
adrenal production of androgens.
The most important issues regarding
the use of combination OCs in the pediatric population involve whether low
doses of estrogen provide sufﬁcient
estrogen for bone accrual and at what
age it is safe to initiate use. Approximately 50% of bone mass is accrued
between the ages of 12 and 18 years.142
Some experts believe that it is important to allow the development of as
much bone mineral density (BMD) as
possible before initiating treatment
with exogenous estrogen.
Although others have antiacne efﬁcacy,
only 3 combination OCs are currently FDA
approved for the treatment of acne
(Ortho Tri Cyclen [norgestimate/ethinyl
estradiol] Tablets indicated for use in
moderate acne in females $15 years
of age; Estrostep [norethindrone acetate
and ethinyl estradiol] Tablets indicated for use in moderate acne for
females $15 years of age; and Yaz
[drospirenone/ethinyl estradiol] Tablets
for moderate acne in females $14 years
of age). The reduction in the estrogen
dosage of OCs has lowered the risk of
thromboembolism associated with some
of the earlier OC formulations, although
this relationship is still under review by
the FDA. Although absolute thromboembolic risk is low in adolescence, it is
recommended that a family history of
thrombotic events be obtained and
young patients are asked if they smoke
before OCs are prescribed. The most
common adverse events related to their
use include nausea/vomiting, breast
tenderness, headache, weight gain, and
breakthrough bleeding.
In a 24-month study of postmenarchal
girls with a mean age of 16.0 6 1.4
years who were treated with an OC
containing 100 mcg levonorgestrel and
20 mcg ethinyl estradiol, there was
a mean increase in lumbar spine BMD
at the femoral neck in 4.2% of girls who
received OC versus 6.3% in untreated
controls.143 The use of OCs did not result in osteopenia in any subject. Nevertheless, the authors concluded that it
is unclear whether the currently
available low-dose OC containing 20
mcg ethinyl estradiol is adequate for
bone mass accrual in this age group. A
long-term study of combined OCs with
calcium supplementation revealed no
effect on BMD after 10 years.144 Referral to an adolescent medicine specialist or gynecologist for management
of OC treatment remains dependent on
the physician’s comfort level.
TABLE 7 Topical Fixed-Dose Combination Prescription Acne Therapies
Product
Active Ingredients and Concentration
Acanya Gel
BenzaClin Gel (generic available)
Benzamycin Gel (generic available)
Duac Gela
Epiduo Gel
Veltin Gel
Ziana Gel
Clindamycin phosphate, 1.2%; BP, 2.5% (aqueous-based)
Clindamycin phosphate, 1%; BP, 5% (aqueous-based)
Erythromycin, 3%; BP, 5% (alcohol-based)
Clindamycin phosphate, 1%; BP, 5% (aqueous-based)
Adapalene, 0.1%; BP, 2.5%
Clindamycin phosphate, 1.2%; Tretinoin, 0.025%
Clindamycin phosphate, 1.2%; Tretinoin, 0.025%
Spironolactone is a synthetic steroidal
androgen receptor blocker that is often
used in female acne patients.145,146 In
select groups of acne patients, spironolactone has revealed efﬁcacy,147–149
although its overall role in acne therapy
and appropriate age to initiate treatment has not yet been fully determined.150 There are minimal data on its
use in pediatric acne.
Consensus Recommendations:
Hormonal therapy with combined
Duac Gel is indicated for inﬂammatory acne vulgaris.
OC may be useful as second-line
therapy in regimens of care in pubertal females with moderate-to-
PEDIATRICS Volume 131, Supplement 3, May 2013
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a
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FIGURE 1
Pediatric treatment recommendations for mild acne.
severe acne. Tobacco use and family
history of thrombotic events should
be assessed. (SOR adolescents: A).
S176
Because of concerns about growth
and bone density, many experts
recommend withholding OC for
acne unassociated with endocrinologic pathology until 1 year after
onset of menstruation. (SOR: C).
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FIGURE 2
Pediatric treatment recommendations for moderate acne.
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FIGURE 3
Pediatric treatment recommendations for severe acne.
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SUPPLEMENT ARTICLE
EVIDENCE-BASED TREATMENT
RECOMMENDATIONS FOR
PEDIATRIC ACNE
When selecting acne treatment, it is
important to assess severity as a function of number, type, and severity of
lesions as well as psychological impact
on the patient including the likelihood of
scarring and/or dyspigmentation. The
panel recommends pediatric treatment
recommendations based on severity of
mild, moderate, and severe acne as
discussed later.
Mild Acne
Mild acne may present as predominantly comedonal or as mixed
comedonal and inﬂammatory disease
(Fig 1). Evidence-based treatment recommendations by the panel for mild
acne are highlighted in Fig 1.
Initial Treatment
antibiotics, and BP as individual
agents or ﬁxed-dose combinations.
(SOR adolescents: A; SOR preadolescents and younger: B).
Inadequate Response
If response to ﬁrst-line treatment is
inadequate, it is important to check
adherence by asking the patient and/or
the parent and, if necessary, to reiterate
usage instructions. If adherence appears to be adequate, a topical retinoid
or BP may be added to monotherapy
with either agent. It has been shown
that early initiation of clindamycin/BP +
adapalene produced earlier and greater
reductions in lesion counts when compared with adapalene monotherapy or
BP/clindamycin for 4 weeks, with adapalene added at week 4.152 The concentration, type, and/or formulation
of the topical retinoid may be changed,
or the topical combination therapy
can be changed. Another option to
consider is topical dapsone; however,
the panel notes large-scale comparative studies of dapsone versus other
topicals are lacking, particularly in pediatric patients.
decades. Physicians may elect to initiate
treatment of moderate acne with
a topical regimen and add an oral antibiotic if the therapeutic response is
not adequate. Alternatively, an oral
antibiotic may be started concomitantly
with a topical regimen for moderate-tosevere acne. Optimally, the topical
regimen would include a retinoid and
a BP-containing formulation, either
separately or as a combination product.
In addition, use of an oral antibiotic may
be especially prudent if there is evidence of acne scarring, even if the
current severity of inﬂammatory acne
is more modest.151 Importantly, some
oral antibiotics, especially tetracycline
derivatives, in addition to antibiotic
activity against P acnes, exhibit certain
antiinﬂammatory and immunomodulatory properties that may be operative
in counteracting mechanisms or pathways involved in acne lesion development.60,153–155
In patients of color in whom the propensity for scarring and PIH is greater,
initial treatment also might include an
oral or topical antibiotic.151 Depending
on patient and parent preference,
treatment could be initiated with
monotherapy, including OTC products.
OTC products are generally effective for
very mild acne, but, with the exception
of BP, data on the efﬁcacy of their
ingredients are lacking. Patients
should be counseled that it takes ∼4 to
8 weeks to demonstrate visible results
from any acne treatment.
Although it is recommended to start
with the least aggressive, effective
regimen, moderate (Fig 2) and severe
acne typically requires a more aggressive regimen, possibly with the
addition of oral antibiotics (Fig 3).
Typically, 4 to 8 weeks of compliant oral
antibiotic use are needed before the
clinical effects of an oral antibiotic are
visible, whereas maximal response may
require 3 to 6 months of administration.15,70 Once the formation of new inﬂammatory lesions, deﬁned as lesions
that are raised by palpation, are
markedly diminished in number, consideration may be given to stopping
oral antibiotics with continuation of
topical therapy to maintain control of
acne.
Initial Therapy
Moderate acne may be initially
Consensus Recommendation:
Overall, oral antibiotic therapy is a safe
and effective approach to the treatment
of moderate-to-severe inﬂammatory or
mixed comedonal and inﬂammatory
acne vulgaris used for more than 5
Topical therapy alone or in combination
is recommended as initial treatment of
mild acne. BP as a single agent, topical
retinoids, or combinations of topical
retinoids, antibiotics, and BP as individual agents or ﬁxed-dose combinations may be used.
Initial therapy for mild acne may
include OTC products such as BP
as a single agent, topical retinoids,
or combinations of topical retinoids,
Moderate Acne
Consensus Recommendation:
Initial therapy for moderate acne may
include topical combination therapies
as described earlier or with combinations that include topical dapsone.
Adding an Oral Antibiotic
treated with topical combinations
including a retinoid and BP and/
or antibiotics, or with oral antibiotics in addition to a topical retinoid
and BP and/or topical antibiotics.
(SOR adolescents: A; SOR preadolescents and younger: C).
Inadequate Response
If response to the above topical combination regimens with or without oral
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S179
antibiotics is inadequate, adherence
should again be evaluated. Referral to
a dermatologist or pediatric dermatologist may be considered if response
has been poor and there is continued
patient or parental frustration. The
type, strength, or formulation of the
retinoid, BP, or BP-antibiotic component
of the topical regimen may be changed
to increase potency or adjusted to reduce skin irritation if present or to
simplify the steps of application.
Severe Acne
Patients with severe acne are at signiﬁcant risk for scarring (Fig 3). The
panel recommends that the prompt
initiation of appropriate treatment is
essential to control the condition and
prevent permanent skin changes.
Initial Treatment
Although the therapeutic agents are the
same as those used in moderate acne, it
is recommended that an oral antibiotic
should be part of the initial treatment
and should be used with either a topical
retinoid + BP with or without topical
antibiotics.
Consensus Recommendation:
Severe acne should be treated with
oral antibiotics and topical retinoids with BP, with or without topical antibiotics, with consideration
of hormonal therapy in pubertal
females, oral isotretinoin, and dermatology referral. (SOR: C).
Inadequate Response
In cases of inadequate response,
compliance with the prescribed regimen should be reassessed ﬁrst. If adherence has been adequate, the oral
antibiotic agent or class may be
changed. For instance, if doxycycline
has provided only a partial response,
minocycline might prove a more effective alternative. For female patients,
combination OC therapy should be
S180
considered. Both male and female
patients unresponsive to these topical
and oral therapies will beneﬁt from
consideration of oral isotretinoin.
RECOMMENDATIONS FOR ACNE
MANAGEMENT IN THE
PREADOLESCENT
The algorithm for acne management of
the preadolescent is essentially the
same as for the adolescent, though
these recommendations are based
more strongly on expert opinion. Antibiotics in the tetracycline class should
not be used for the treatment of acne in
patients under 8 years of age.
OTHER CONSIDERATIONS FOR
PEDIATRIC ACNE TREATMENT
SELECTION
A number of additional considerations
are pertinent to acne management
and selection of therapies in pediatric
patients. Chief among them are an
understanding of previous treatment
history, cost of medications, ease of use
and regimen complexity and its impact
on adherence, vehicle selection, active
scarring, and psychosocial impact of
the acne on the individual. In addition,
the inﬂuence of diet on acne, an area of
evolving understanding, may be considered.
Previous Treatment and History
At the initial assessment, it is crucial to
inquire about previous treatment history, if any. An important question is
whether the patient responded to
a speciﬁc ﬁrst-line regimen. If so, unless
there are circumstances dictating
otherwise, treatment should be reinitiated with the previous regimen or
some of its elements. However, if response to previous therapies has been
poor, up-titration, add-on therapies, or
switching to an alternative should be
considered.156
Financial Costs
In addition to the aforementioned
considerations, patient resources and
the ﬁnancial costs of treatment must be
considered when selecting a treatment
regimen from the panel recommendations. A recent retrospective crosssectional study by Patel et al157 of 3
784 816 patients with acne and similar
conditions indicated there was a signiﬁcant overall decrease in reported
total annual prescription spending
widely attributed to the reduction of
oral antibiotic use and increase in the
use of OCs and oral retinoids. Further,
the use of topical retinoids was preferred in combination with other treatments rather than as monotherapy.
Managed-care organizations are increasingly requiring cost-sharing, and
it may be necessary to adapt prescribing preferences to patient resources.
Ease of Use, Regimen Complexity,
and Adherence
Adherence is the contemporary terminology for persistence in use of a recommended medical treatment and
denotes a partnership between the
patient and the physician. Adherence
with an acne treatment regimen is a sine
qua non of successful management. In
fact, lack of adherence is a major reason
for acne treatment failures.158 Prevention and proactive education is easier
than dealing with nonadherence after
treatment response has been inadequate.5 Therefore, adherence to the
prescribed regimen should be assessed at each visit, particularly if the
response is less than expected. Adherence is a function of cost of medications/
therapies, ease of use/regimen simplicity, patient preferences, tolerability,
rapidity of results, and patient or parent understanding.
Vehicle Selection
In 1 small study, it was found that
nonadherence with acne treatment was
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SUPPLEMENT ARTICLE
52% after 3 months.159 Adherence may
be improved through patient and parent
education, selection of a simple regimen, more frequent doctor visits, and
choice of vehicles that improve medication tolerability. One study revealed a direct correlation between adherence and
dosing frequency, with 83.6% of patients
complying with once-daily dosing versus
74.9% with twice-daily dosing. Fixed
combinations of topical medications
may be helpful in this regard.
Empowering patients with control over
their care is important for adherence.160 It is essential to elicit information at each doctor visit about patient
preferences and lifestyle. For example,
a water-based gel may be the optimal
choice for the patient who wears
makeup.161 Teenagers, especially males,
may not like the feel of moisturizers but
may accept a gel, pad or foam, or inshower wash.160 Other vehicle considerations center around tolerability,
which is inﬂuenced by the medication’s
impact on the skin barrier. Many topical
medications are being formulated in
vehicles, including aqueous gels, which
are therapeutic and may help rehydrate
and repair the skin barrier.161 It may be
useful to initiate treatment with extremely mild topical agents until the
skin has adjusted to medication effects
and patients have adapted to side
effects.160
Active Scarring
The likelihood of scarring is an important consideration in treatment
selection. Patients with moderate and
severe acne are at increased risk of
scarring, as are those with more deeply
pigmented skin.151 Hence, aggressive
treatment is warranted to prevent
permanent sequelae in these patient
populations.
Psychosocial Impact
The psychosocial impact of acne is inﬂuenced by numerous factors including
age, disease severity, social and familial
networks, and individual personalities.
Adolescents with substantial acne are
reported to have high rates of mental
health problems, affective isolation,
social impairment, depression, and
suicidal ideation.162 In the cases where
the impact on the psychosocial health
of the patient is particularly burdensome, effective treatment of acne may
result in improvements in self-esteem,
affect, shame, embarrassment, body
image, social assertiveness, and selfconﬁdence.150
Managing Expectations
Adolescents are notoriously impatient.
Physicians, who see the patient at
intervals rather than daily, may note
improvement between visits that may
not be readily apparent to the adolescent who examines his or her face in the
mirror several times per day.156 A basic
understanding of acne pathophysiology and how prescribed agents work
to control acne may augment adherence.163 For example, both patients and
parents should be given reasonable
expectations of the time to visible improvement. It is important to explain
that acne may worsen or irritation may
be more signiﬁcant initially, with gradual
improvement. An understanding of the
“invisible microcomedo” helps patients
understand why topical medications
should be applied to the entire face.
Many adolescents believe that acne is
related to facial hygiene, and so they
may try treating themselves with harsh
astringents, abrasives, or vigorous
scrubbing. It is important for them to
understand that such treatment may
actually worsen theiracne and increase
the likelihood of inﬂammation and
scarring. Many clinicians prefer to recommend an appropriate gentle, daily
skin-care regimen, including a noncomedogenic moisturizer and sunscreen for the patient to use with the
prescribed treatment(s).
Diet and Acne
Consideration of a role for diet in contributing to acne arose in the 1930s, and
chocolate, sugar, and iodine were
among the dietary factors implicated.
As a result of a series of studies in the
late 1960s that failed to identify a dietary
connection, the concept fell out of
fashion.164 However, the debate has
been rekindled in response to a variety
of data emerging over the last decade.
A retrospective recall-based study in
adult nurses165 and a prospective selfassessment study in teenage girls166
both suggested an association between acne and intake of milk and
other dairy products. A subsequent
prospective study in teenage boys
suggested an association with skim
milk,167 although the previous 2 studies
did not identify a difference based on
milk fat content.
The effects on acne of glycemic load in
the diet also have been subjected to
examination. An anthropologic study168
comparing acne rates in a huntergatherer population in Papua New
Guinea versus those in the developed
world suggested that dietary glycemic
load may contribute to the observed
differences in acne incidence. A number of prospective trials169,170 subsequently have been performed,
notably including a randomized prospective controlled trial of a low glycemic diet versus a high glycemic diet
in teenage boys.171 By the end of the
12-week study, the low glycemic diet
was shown to provide superior reduction in the number of total acne lesions
(223.5 6 3.9 vs 212.0 6 3.5, P = .03),
as well as reductions in inﬂammatory
lesion count and other parameters including weight and BMI.
Other dietary constituents that are the
subject of renewed interest include zinc
and antioxidants; the role of chocolate
is being reinvestigated in a blinded
placebo-controlled clinical trial (clinicaltrials.gov). Based on the currently
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S181
CONCLUSIONS
same principles and therapeutic agents
apply to all age groups diagnosed with
acne. However, age group differences
may require special considerations in
the use of these agents, particularly
with regard to ease of use and patient
adherence, cost factors, differences in
psychosocial impacts among age
groups, the likelihood of scarring, and
the use of advanced vehicles to minimize adverse effects on young skin.
As the pathogenesis of acne vulgaris
appears to be similar at all ages, the
Although there are many acne treatment approaches to consider, these
evidence-based treatment recommendations from the pediatric perspective
may provide useful guidance in the
management of acne vulgaris during
childhood and adolescence. In most
cases, acne can be successfully treated
by nondermatologists. In other instances, clinicians may decide that, in addition to using these recommendations,
consultation with another specialist
such as a pediatric dermatologist or
pediatric endocrinologist is appropriate.
11. Marcoux D, McCuaig CC, Powell J. Prepubertal acne: clinical presentation,
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12. Cunliffe WJ, Baron SE, Coulson IH. A clinical and therapeutic study of 29 patients
with infantile acne. Br J Dermatol. 2001;
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13. Herane MI, Ando I. Acne in infancy and acne
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14. Lucky AW, Koltun W, Thiboutot D, et al. A
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certainty to any dietary manipulation
that should be recommended to pediatric patients suffering from acne;
however, consideration may be given in
individual cases to institution of a low
glycemic diet. Patient and parent education to dispel acne myths is an important treatment consideration.
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ABBREVIATIONS
AARS—American Acne and Rosacea Society
BIH—benign intracranial hypertension
BMD—bone mineral density
BP—benzoyl peroxide
DHS—drug hypersensitivity syndrome
FDA—Food and Drug Administration
IBD—inﬂammatory bowel disease
LLS—lupuslike syndrome
NCP—neonatal cephalic pustulosis
OC—oral contraceptive
OTC—over-the-counter
PCOS—polycystic ovary syndrome
PIH—postinﬂammatory hyperpigmentation
SOR—Strength of Recommendation
www.pediatrics.org/cgi/doi/10.1542/peds.2013-0490B
doi:10.1542/peds.2013-0490B
Accepted for publication Feb 21, 2013
Address correspondence to Lawrence F. Eichenﬁeld, MD, 8010 Frost Street, Ste 602, San Diego, CA 92130. E-mail: leichenﬁeld@rchsd.org
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).
Copyright © 2013 by the American Academy of Pediatrics
FINANCIAL DISCLOSURE: All authors ﬁled relevant conﬂicts of interest statements with the American Acne and Rosacea Society (AARS) and the American Academy
of Pediatrics (AAP). They received compensation from the AARS for participation in this consensus conference. Their participation included preparatory
conference calls, planning communications, extensive literature search and research on subject, preparation of presentations including slides, and manuscript
development, writing, and editing. No corporate benefactor of the AARS or AAP had any input into content preparation, data review, or any involvement in the
outcome of the meeting or publication. Physician Resources, LLC provided editorial and research assistance to the AARS throughout the process.
FUNDING: The AARS, a nonproﬁt organization, received educational grant funding from annual corporate benefactors to fund this article. Those benefactors
include Galderma Laboratories, Medicis Pharmaceuticals, Ortho Dermatologics, and Valeant Pharmaceuticals. No corporate benefactor of the AARS or AAP had any
input into content preparation or data review, or any involvement in the outcome of the meeting or publication.
S186
EICHENFIELD et al
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Evidence-Based Recommendations for the Diagnosis and Treatment of Pediatric
Acne
Lawrence F. Eichenfield, Andrew C. Krakowski, Caroline Piggott, James Del Rosso,
Hilary Baldwin, Sheila Fallon Friedlander, Moise Levy, Anne Lucky, Anthony J.
Mancini, Seth J. Orlow, Albert C. Yan, Keith K. Vaux, Guy Webster, Andrea L.
Zaenglein and Diane M. Thiboutot
Pediatrics 2013;131;S163
DOI: 10.1542/peds.2013-0490B
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